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Cambridge quarterly of healthcare ethic... Publications | PubFacts

178,865 results match your criteria Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees[Journal]


Therapeutic Approaches To Enhance PINK1/Parkin Mediated Mitophagy For The Treatment Of Parkinson's Disease.

Neurosci Lett 2019 Apr 14. Epub 2019 Apr 14.

MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dow St, Dundee, DD1 5EH, Scotland.

The discovery of rare familial monogenic forms of early-onset Parkinson's disease has led to the identification of a mitochondrial quality control process as a key player in this disease. Loss-of-function mutations in the genes encoding PINK1 or Parkin result in insufficient removal of dysfunctional mitochondria through autophagy, a process termed mitophagy. Understanding the mechanism of this process and the function of its two key players, PINK1 and Parkin, has led to the discovery of new therapeutic approaches. Read More

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http://dx.doi.org/10.1016/j.neulet.2019.04.029DOI Listing

Immune Signaling in Neurodegeneration.

Immunity 2019 Apr;50(4):955-974

Boston Children's Hospital, F.M. Kirby Neurobiology Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address:

Neurodegenerative diseases of the central nervous system progressively rob patients of their memory, motor function, and ability to perform daily tasks. Advances in genetics and animal models are beginning to unearth an unexpected role of the immune system in disease onset and pathogenesis; however, the role of cytokines, growth factors, and other immune signaling pathways in disease pathogenesis is still being examined. Here we review recent genetic risk and genome-wide association studies and emerging mechanisms for three key immune pathways implicated in disease, the growth factor TGF-β, the complement cascade, and the extracellular receptor TREM2. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.016DOI Listing

GM-CSF, IL-3, and IL-5 Family of Cytokines: Regulators of Inflammation.

Immunity 2019 Apr;50(4):796-811

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA. Electronic address:

The β common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmune disease, and others show promising early clinical activity. These approaches are based on our understanding of the inflammatory roles of these cytokines; however, GM-CSF also participates in the resolution of inflammation, and IL-3 and IL-5 may also have such properties. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.022DOI Listing

A Comprehensive Drosophila melanogaster Transcription Factor Interactome.

Cell Rep 2019 Apr;27(3):955-970.e7

Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Bioinformatics and Integrative Genomics Ph.D. Program, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.071DOI Listing

Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.

Cell Rep 2019 Apr;27(3):806-819.e5

Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

KRAS is one of the driver oncogenes in non-small-cell lung cancer (NSCLC) but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and enables their proliferation. Two MEKis, selumetinib and trametinib, induce T cell activation with increased CTLA-4 expression and, to a lesser extent, PD-1 expression on T cells in vivo after cyclical pulsatile MEKi treatment. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.066DOI Listing

The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.

Cell Rep 2019 Apr;27(3):776-792.e7

Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA. Electronic address:

Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.063DOI Listing

Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism.

Cell Rep 2019 Apr;27(3):750-761.e7

Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil. Electronic address:

Antibiotic-induced dysbiosis is a key factor predisposing intestinal infection by Clostridium difficile. Here, we show that interventions that restore butyrate intestinal levels mitigate clinical and pathological features of C. difficile-induced colitis. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.054DOI Listing

lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation.

Cell Rep 2019 Apr;27(3):719-729.e6

Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; New York Genome Center, New York, NY 10013, USA. Electronic address:

Long non-coding RNAs (lncRNAs) show patterns of tissue- and cell type-specific expression that are very similar to those of protein coding genes and consequently have the potential to control stem and progenitor cell fate decisions along a differentiation trajectory. To understand the roles that lncRNAs may play in hematopoiesis, we selected a subset of mouse lncRNAs with potentially relevant expression patterns and refined our candidate list using evidence of conserved expression in human blood lineages. For each candidate, we assessed its possible role in hematopoietic differentiation in vivo using competitive transplantation. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.080DOI Listing

Adverse risk factor trends limit gains in coronary heart disease mortality in Barbados: 1990-2012.

PLoS One 2019 17;14(4):e0215392. Epub 2019 Apr 17.

Population Health Research Institute, St. George's, University of London, London, United Kingdom.

Background: Although most countries face increasing population levels of obesity and diabetes their effect on coronary heart disease (CHD) mortality has not been often studied in small island developing states (SIDs) where obesity rates are among the highest in the world. We estimated the relative contributions of treatments and cardiovascular risk factors to the decline in CHD mortality from 1990 to 2012 in the Caribbean island, Barbados.

Methods: We used the IMPACT CHD mortality model to estimate the effect of increased coverage of effective medical/surgical treatments and changes in major CHD risk factors on mortality trends in 2012 compared with 1990. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215392PLOS

What do cost-effective health behaviour-change interventions contain? A comparison of six domains.

PLoS One 2019 17;14(4):e0213983. Epub 2019 Apr 17.

Department of Behavioural Science and Health, University College London, London, United Kingdom.

Objectives: To help implement behaviour change interventions (BCIs) in practice it is important to be able to characterize their key components. This study compared broad features of cost-effective BCIs that addressed smoking, diet, physical activity, alcohol and sexual health. It also assessed the association of these with the magnitude of the cost-effectiveness estimates. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213983PLOS

Identifying Developmental Language Disorder in Vietnamese Children.

J Speech Lang Hear Res 2019 Apr 17:1-16. Epub 2019 Apr 17.

San Diego State University, CA.

Purpose Developmental language disorder (DLD), defined by low language performance despite otherwise normal development, can negatively impact children's social and academic outcomes. This study is the 1st to examine DLD in Vietnamese. To lay the foundation, we identified cases of DLD in Vietnam and explored language-specific characteristics of the disorder. Read More

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http://dx.doi.org/10.1044/2019_JSLHR-L-18-0305DOI Listing

The Human Lung Cell Atlas - A high-resolution reference map of the human lung in health and disease.

Am J Respir Cell Mol Biol 2019 Apr 17. Epub 2019 Apr 17.

University of Groningen, University Medical Center Groningen, Pathology and Medical Biology, Groningen, Netherlands.

Lung disease accounts for every sixth death globally. Profiling the molecular state of all lung cell types in health and disease is currently revolutionizing the identification of disease mechanisms and will aid the design of novel diagnostic and personalized therapeutic regimens. Recent progress in high-throughput techniques for single-cell genomic and transcriptomic analyses has opened up new possibilities to study individual cells within a tissue, classify these into cell types, and characterize variations in their molecular profiles as a function of genetics, environment, cell-cell interactions, developmental processes, ageing or disease. Read More

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https://www.atsjournals.org/doi/10.1165/rcmb.2018-0416TR
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http://dx.doi.org/10.1165/rcmb.2018-0416TRDOI Listing
April 2019
1 Read

Azaindenocorannulenes: Synthesis, Properties, and Chirality.

Org Lett 2019 Apr 17. Epub 2019 Apr 17.

Health Science Platform , Tianjin University , 92 Weijin Road , Nankai District, Tianjin 300072 , P. R. China.

Palladium-catalyzed intramolecular arylation provides bowl-shaped azaindenocorannulenes 7-9. Crystals of 8 show bowl-in-bowl columnar stacking. A substituent model rationalizes the first reduction potential of 18 related molecular bowls. Read More

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http://pubs.acs.org/doi/10.1021/acs.orglett.9b00718
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http://dx.doi.org/10.1021/acs.orglett.9b00718DOI Listing
April 2019
1 Read

Nanowired Bioelectric Interfaces.

Chem Rev 2019 Apr 17. Epub 2019 Apr 17.

Department of Chemistry and Chemical Biology , Harvard University , Cambridge , Massachusetts 02138 , United States.

Biological systems have evolved biochemical, electrical, mechanical, and genetic networks to perform essential functions across various length and time scales. High-aspect-ratio biological nanowires, such as bacterial pili and neurites, mediate many of the interactions and homeostasis in and between these networks. Synthetic materials designed to mimic the structure of biological nanowires could also incorporate similar functional properties, and exploiting this structure-function relationship has already proved fruitful in designing biointerfaces. Read More

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http://dx.doi.org/10.1021/acs.chemrev.8b00795DOI Listing

Telehealth-Based Health Coaching Increases m-Health Device Adherence and Rate of Weight Loss in Obese Participants.

Telemed J E Health 2019 Apr 17. Epub 2019 Apr 17.

1 Department of Kinesiology, California State University, Long Beach, Long Beach, California.

t χ Read More

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http://dx.doi.org/10.1089/tmj.2019.0017DOI Listing

The pathway and kinetics of hierarchical assembly of ionic oligomers into a lyotropic columnar phase.

Soft Matter 2019 Apr 17. Epub 2019 Apr 17.

National Synchrotron Radiation Lab, University of Science and Technology of China, Hefei, China.

Ionic benzene-1,3,5-tricarboxamide (BTA) molecules can self-assemble into hollow cylinders which further arrange into columnar phases in water. In situ investigations suggest a multi-step pathway of supramolecular assembly via formation of dispersed molecular aggregates followed by a less ordered intermediate phase before the equilibrium columnar phase is formed. The pathway and kinetics of the formation of lyotropic LC phases through hierarchical supramolecular assembly are similar to non-classical crystallization, in line with an emerging holistic view on crystallization and self-assembly. Read More

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http://dx.doi.org/10.1039/c9sm00383eDOI Listing

A Prospective Study on the Impact and Out-of-Pocket Costs of Dengue Illness in International Travelers.

Am J Trop Med Hyg 2019 Apr 15. Epub 2019 Apr 15.

Department of Disease Control, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Although the costs of dengue illness to patients and households have been extensively studied in endemic populations, international travelers have not been the focus of costing studies. As globalization and human travel activities intensify, travelers are increasingly at risk for emerging and reemerging infectious diseases, such as dengue. This exploratory study aims to investigate the impact and out-of-pocket costs of dengue illness among travelers. Read More

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http://dx.doi.org/10.4269/ajtmh.18-0780DOI Listing

Emotion sensitivity and self-reported symptoms of generalized anxiety disorder across the lifespan: A population-based sample approach.

Brain Behav 2019 Apr 16:e01282. Epub 2019 Apr 16.

Institute for Technology in Psychiatry, McLean Hospital, Belmont, Massachusetts.

Background: Individuals with generalized anxiety disorder (GAD) symptoms show deficits in emotion processing, but results of prior studies have been conflicting, and little is known about developmental trajectories of emotion processing over time. We examined the association between GAD symptoms and sensitivity to recognizing emotional facial expressions (emotion sensitivity: ES) for three emotions (happiness, anger, fear) in a large, diverse, population-based sample. We hypothesized that higher anxiety scores would be associated with poorer performance, and expected that ES performance and anxiety scores would decline across the lifespan. Read More

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http://dx.doi.org/10.1002/brb3.1282DOI Listing

Mental health and behavioural problems in children with XXYY: a comparison with intellectual disabilities.

J Intellect Disabil Res 2019 May;63(5):477-488

Great Ormond Street Institute of Child Health, University College London, London, UK.

Background: The phenotype of children with XXYY has predominantly been defined by comparison to other sex chromosome aneuploidies trisomies affecting male children; however, the intellectual ability of children with XXYY is lower than children with other sex chromosome aneuploidies trisomies. It is not known to what extent the phenotype identified to date is specific to XXYY, rather than a reflection of lower IQ. This study evaluates the mental health and behaviour of children with XXYY, in comparison to children with intellectual disabilities of heterogeneous genetic origin. Read More

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http://dx.doi.org/10.1111/jir.12607DOI Listing

Dementia Friendly Communities in England: A scoping study.

Int J Geriatr Psychiatry 2019 Apr 16. Epub 2019 Apr 16.

University of Hertfordshire, Hatfield, UK.

Objectives: To describe the characteristics of Dementia Friendly Communities (DFCs) across England, in order to inform a national evaluation of their impact on the lives of those affected by dementia.

Methods: DFCs in England were identified through online searches and Alzheimer's Society records. A sub-sample (n=100) were purposively selected for in-depth study based on online searches and, where necessary, follow-up telephone calls. Read More

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http://dx.doi.org/10.1002/gps.5123DOI Listing

Inflammation in Mild Cognitive Impairment due to Parkinson's disease, Lewy Body disease and Alzheimer's disease.

Int J Geriatr Psychiatry 2019 Apr 16. Epub 2019 Apr 16.

Institute of Neuroscience, Newcastle upon Tyne, United Kingdom.

Background: Inflammation appears to play a role in the progression of neurodegenerative diseases. However, little is known about inflammation during early stages of cognitive decline or whether this differs in different disease groups. We sought to investigate this by assessing the inflammatory profile in patients with Parkinson's disease with the early stages of cognitive impairment (PD-MCI), patients with prodromal Alzheimer's disease (MCI-AD), prodromal Lewy Body disease (MCI-LB) and controls. Read More

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http://dx.doi.org/10.1002/gps.5124DOI Listing

Scaling of cardiac morphology is interrupted by birth in the developing sheep Ovis aries.

J Anat 2019 Apr 17. Epub 2019 Apr 17.

Department of Zoological Sciences, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Scaling of the heart across development can reveal the degree to which variation in cardiac morphology depends on body mass. In this study, we assessed the scaling of heart mass, left and right ventricular masses, and ventricular mass ratio, as a function of eviscerated body mass across fetal and postnatal development in Horro sheep Ovis aries (~50-fold body mass range; N = 21). Whole hearts were extracted from carcasses, cleaned, dissected into chambers and weighed. Read More

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http://dx.doi.org/10.1111/joa.12990DOI Listing

Model-Based Meta-Analysis: Optimizing Research, Development and Utilization of Therapeutics using the Totality of Evidence.

Clin Pharmacol Ther 2019 Apr 16. Epub 2019 Apr 16.

Quantitative Clinical Pharmacology, Takeda Pharmaceuticals International Co, Cambridge, MA, USA.

Model-Based Meta-Analysis (MBMA) is a valuable component of the quantitative pharmacology toolkit for model-informed drug discovery and development. It enables principled decision-making with a Totality of Evidence mindset through integration of internal and external data across multiple dimensions (e.g. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1462
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http://dx.doi.org/10.1002/cpt.1462DOI Listing
April 2019
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Trends in phenotype in the English paediatric Neurofibromatosis Type 2 cohort stratified by genetic severity.

Clin Genet 2019 Apr 16. Epub 2019 Apr 16.

Oxford NF2 Unit, Oxford University Hospitals NHS Foundation Trust.

Childhood onset neurofibromatosis type 2 can be severe and genotype dependent. We present a retrospective phenotypic analysis of all ascertained children in England Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.13551
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http://dx.doi.org/10.1111/cge.13551DOI Listing
April 2019
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Inhibitory Effect of Vonoprazan on the Metabolism of [C]Prasugrel in Human Liver Microsomes.

Eur J Drug Metab Pharmacokinet 2019 Apr 16. Epub 2019 Apr 16.

Global Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., 35 Landsdowne Street, Cambridge, MA, 02139, USA.

Background And Objectives: A recent report indicated that the pharmacodynamic interaction between clopidogrel and vonoprazan leading to attenuation of the anti-platelet effect of clopidogrel was unlikely to be caused by the inhibition of cytochrome P450 (CYP) 2B6, CYP2C19, or CYP3A4/5 by vonoprazan, based on in vitro CYP inhibition data. The current report investigates another important antiplatelet inhibitor, prasugrel, that is also activated through metabolism by CYP2B6, CYP2C19 and CYP3A4/5, for its CYP-based DDI potential with vonoprazan. The report describes in vitro metabolic inhibition assessments using radiolabeled prasugrel and human liver microsomes (HLMs). Read More

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http://dx.doi.org/10.1007/s13318-019-00554-yDOI Listing

Do Immediate Gains Predict Long-Term Symptom Change? Findings from a Randomized Trial of a Single-Session Intervention for Youth Anxiety and Depression.

Child Psychiatry Hum Dev 2019 Apr 16. Epub 2019 Apr 16.

Psychology Department, Harvard University, Cambridge, USA.

Single-session interventions (SSIs) can help reduce youth psychopathology, but SSIs may benefit some youths more than others. Identifying predictors of SSIs' effectiveness may clarify youths' likelihoods of benefitting from an SSI alone, versus requiring further treatment. We tested whether pre-to-post-SSI shifts in hypothesized symptom change mechanisms predicted subsequent reductions in youth internalizing symptoms. Read More

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http://dx.doi.org/10.1007/s10578-019-00889-2DOI Listing

Can we reduce the workload of mammographic screening by automatic identification of normal exams with artificial intelligence? A feasibility study.

Eur Radiol 2019 Apr 16. Epub 2019 Apr 16.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Purpose: To study the feasibility of automatically identifying normal digital mammography (DM) exams with artificial intelligence (AI) to reduce the breast cancer screening reading workload.

Methods And Materials: A total of 2652 DM exams (653 cancer) and interpretations by 101 radiologists were gathered from nine previously performed multi-reader multi-case receiver operating characteristic (MRMC ROC) studies. An AI system was used to obtain a score between 1 and 10 for each exam, representing the likelihood of cancer present. Read More

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http://link.springer.com/10.1007/s00330-019-06186-9
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http://dx.doi.org/10.1007/s00330-019-06186-9DOI Listing
April 2019
1 Read

Engineering phonon polaritons in van der Waals heterostructures to enhance in-plane optical anisotropy.

Sci Adv 2019 Apr 12;5(4):eaau7171. Epub 2019 Apr 12.

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.

Van der Waals (vdW) heterostructures assembled from layers of two-dimensional materials have attracted considerable interest due to their novel optical and electrical properties. Here, we report a scattering-type scanning near-field optical microscopy study of hexagonal boron nitride on black phosphorus (h-BN/BP) heterostructures, demonstrating the first direct observation of in-plane anisotropic phonon polariton modes in vdW heterostructures. Notably, the measured in-plane optical anisotropy along the armchair and zigzag crystal axes exceeds the ratio of refractive indices of BP in the - plane. Read More

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http://dx.doi.org/10.1126/sciadv.aau7171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461454PMC

Chemogenetics defines receptor-mediated functions of short chain free fatty acids.

Nat Chem Biol 2019 May 15;15(5):489-498. Epub 2019 Apr 15.

Centre for Translational Pharmacology, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Differentiating actions of short chain fatty acids (SCFAs) at free fatty acid receptor 2 (FFA2) from other free fatty acid-responsive receptors and from non-receptor-mediated effects has been challenging. Using a novel chemogenetic and knock-in strategy, whereby an engineered variant of FFA2 (FFA2-DREADD) that is unresponsive to natural SCFAs but is instead activated by sorbic acid replaced the wild-type receptor, we determined that activation of FFA2 in differentiated adipocytes and colonic crypt enteroendocrine cells of mouse accounts fully for SCFA-regulated lipolysis and release of the incretin glucagon-like peptide-1 (GLP-1), respectively. In vivo studies confirmed the specific role of FFA2 in GLP-1 release and also demonstrated a direct role for FFA2 in accelerating gut transit. Read More

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http://www.nature.com/articles/s41589-019-0270-1
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http://dx.doi.org/10.1038/s41589-019-0270-1DOI Listing
May 2019
1 Read

CRISPR-suppressor scanning reveals a nonenzymatic role of LSD1 in AML.

Nat Chem Biol 2019 May 15;15(5):529-539. Epub 2019 Apr 15.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

Understanding the mechanism of small molecules is a critical challenge in chemical biology and drug discovery. Medicinal chemistry is essential for elucidating drug mechanism, enabling variation of small molecule structure to gain structure-activity relationships (SARs). However, the development of complementary approaches that systematically vary target protein structure could provide equally informative SARs for investigating drug mechanism and protein function. Read More

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http://dx.doi.org/10.1038/s41589-019-0263-0DOI Listing

Author Correction: Novel electrode technologies for neural recordings.

Nat Rev Neurosci 2019 Apr 16. Epub 2019 Apr 16.

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

In part b of Figure 2 in this article, the left bounds of the boxes representing the spatiotemporal resolution of 'EEG/MEG' and 'ECoG' were incorrect. Specifically, the limits of highest temporal resolution for EEG/MEG and ECoG were shown as ~200 ms and ~10 ms and are now corrected to ~2 ms and < 1 ms, respectively. In addition, the lower bounds of the boxes representing 'fMRI/PET' and 'EEG/MEG' incorrectly showed the highest spatial resolution limits of these technologies as ~1 mm and have been corrected to <1 mm and <10 mm, respectively. Read More

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http://dx.doi.org/10.1038/s41583-019-0169-6DOI Listing

Bioproduction of pure, kilobase-scale single-stranded DNA.

Sci Rep 2019 Apr 16;9(1):6121. Epub 2019 Apr 16.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Scalable production of kilobase single-stranded DNA (ssDNA) with sequence control has applications in therapeutics, gene synthesis and sequencing, scaffolded DNA origami, and archival DNA memory storage. Biological production of circular ssDNA (cssDNA) using M13 addresses these needs at low cost. However, one unmet goal is to minimize the essential protein coding regions of the exported DNA while maintaining its infectivity and production purity to produce sequences less than 3,000 nt in length, relevant to therapeutic and materials science applications. Read More

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http://dx.doi.org/10.1038/s41598-019-42665-1DOI Listing

Analysis of tractable allosteric sites in G protein-coupled receptors.

Sci Rep 2019 Apr 16;9(1):6180. Epub 2019 Apr 16.

Medicinal Chemistry Research Group, Research Center for Natural Sciences, Magyar tudósok krt. 2, H-1117, Budapest, Hungary.

Allosteric modulation of G protein-coupled receptors represent a promising mechanism of pharmacological intervention. Dramatic developments witnessed in the structural biology of membrane proteins continue to reveal that the binding sites of allosteric modulators are widely distributed, including along protein surfaces. Here we restrict consideration to intrahelical and intracellular sites together with allosteric conformational locks, and show that the protein mapping tools FTMap and FTSite identify 83% and 88% of such experimentally confirmed allosteric sites within the three strongest sites found. Read More

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http://dx.doi.org/10.1038/s41598-019-42618-8DOI Listing

Multi-platform discovery of haplotype-resolved structural variation in human genomes.

Nat Commun 2019 Apr 16;10(1):1784. Epub 2019 Apr 16.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.

The incomplete identification of structural variants (SVs) from whole-genome sequencing data limits studies of human genetic diversity and disease association. Here, we apply a suite of long-read, short-read, strand-specific sequencing technologies, optical mapping, and variant discovery algorithms to comprehensively analyze three trios to define the full spectrum of human genetic variation in a haplotype-resolved manner. We identify 818,054 indel variants (<50 bp) and 27,622 SVs (≥50 bp) per genome. Read More

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http://www.nature.com/articles/s41467-018-08148-z
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http://dx.doi.org/10.1038/s41467-018-08148-zDOI Listing
April 2019
1 Read

Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells.

Nat Commun 2019 Apr 16;10(1):1763. Epub 2019 Apr 16.

Biological and Soft Systems Sector, Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, UK.

Personalized approaches for systematically assessing ciliary beat dynamics and for drug testing would improve the challenging task of diagnosing and treating respiratory disorders. In this pilot study, we show how multiscale differential dynamic microscopy (multi-DDM) can be used to characterize collective ciliary beating in a non-biased automated manner. We use multi-DDM to assess the efficacy of different CFTR-modulating drugs in human airway epithelial cells derived from subjects with cystic fibrosis (ΔF508/ΔF508 and ∆F508/-) based on ciliary beat frequency and coordination. Read More

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http://www.nature.com/articles/s41467-019-09798-3
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http://dx.doi.org/10.1038/s41467-019-09798-3DOI Listing
April 2019
1 Read

Polygenic prediction via Bayesian regression and continuous shrinkage priors.

Nat Commun 2019 Apr 16;10(1):1776. Epub 2019 Apr 16.

Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.

Polygenic risk scores (PRS) have shown promise in predicting human complex traits and diseases. Here, we present PRS-CS, a polygenic prediction method that infers posterior effect sizes of single nucleotide polymorphisms (SNPs) using genome-wide association summary statistics and an external linkage disequilibrium (LD) reference panel. PRS-CS utilizes a high-dimensional Bayesian regression framework, and is distinct from previous work by placing a continuous shrinkage (CS) prior on SNP effect sizes, which is robust to varying genetic architectures, provides substantial computational advantages, and enables multivariate modeling of local LD patterns. Read More

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http://dx.doi.org/10.1038/s41467-019-09718-5DOI Listing

Learning about climate change uncertainty enables flexible water infrastructure planning.

Nat Commun 2019 Apr 16;10(1):1782. Epub 2019 Apr 16.

Joint Program on the Science and Policy of Global Change, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E19-411, Cambridge, MA, 02139, USA.

Water resources planning requires decision-making about infrastructure development under uncertainty in future regional climate conditions. However, uncertainty in climate change projections will evolve over the 100-year lifetime of a dam as new climate observations become available. Flexible strategies in which infrastructure is proactively designed to be changed in the future have the potential to meet water supply needs without expensive over-building. Read More

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http://dx.doi.org/10.1038/s41467-019-09677-xDOI Listing

Microbial and metabolic succession on common building materials under high humidity conditions.

Nat Commun 2019 Apr 16;10(1):1767. Epub 2019 Apr 16.

Department of Pediatrics and Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, 92037, USA.

Despite considerable efforts to characterize the microbial ecology of the built environment, the metabolic mechanisms underpinning microbial colonization and successional dynamics remain unclear, particularly at high moisture conditions. Here, we applied bacterial/viral particle counting, qPCR, amplicon sequencing of the genes encoding 16S and ITS rRNA, and metabolomics to longitudinally characterize the ecological dynamics of four common building materials maintained at high humidity. We varied the natural inoculum provided to each material and wet half of the samples to simulate a potable water leak. Read More

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http://dx.doi.org/10.1038/s41467-019-09764-zDOI Listing

Nanostructured polymer films with metal-like thermal conductivity.

Nat Commun 2019 Apr 16;10(1):1771. Epub 2019 Apr 16.

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Due to their unique properties, polymers - typically thermal insulators - can open up opportunities for advanced thermal management when they are transformed into thermal conductors. Recent studies have shown polymers can achieve high thermal conductivity, but the transport mechanisms have yet to be elucidated. Here we report polyethylene films with a high thermal conductivity of 62 Wm K, over two orders-of-magnitude greater than that of typical polymers (~0. Read More

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http://www.nature.com/articles/s41467-019-09697-7
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http://dx.doi.org/10.1038/s41467-019-09697-7DOI Listing
April 2019
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Radiocarbon dating the end of urban services in a late Roman town.

Proc Natl Acad Sci U S A 2019 Apr 16. Epub 2019 Apr 16.

Initiative for the Science of the Human Past at Harvard, Department of History, Harvard University, Cambridge, MA 02138;

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http://dx.doi.org/10.1073/pnas.1904037116DOI Listing

Testing the role of trait reversal in evolutionary diversification using song loss in wild crickets.

Proc Natl Acad Sci U S A 2019 Apr 16. Epub 2019 Apr 16.

School of Life Sciences, University of Lincoln, Lincoln LN6 7DL, United Kingdom

The mechanisms underlying rapid macroevolution are controversial. One largely untested hypothesis that could inform this debate is that evolutionary reversals might release variation in vestigial traits, which then facilitates subsequent diversification. We evaluated this idea by testing key predictions about vestigial traits arising from sexual trait reversal in wild field crickets. Read More

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http://dx.doi.org/10.1073/pnas.1818998116DOI Listing

Portal pyaemia secondary to colonic perforation.

BMJ Case Rep 2019 Apr 15;12(4). Epub 2019 Apr 15.

Department of Hepatopancreaticobiliary Surgery, Cambridge University Hospital, Cambridge, Cambridgeshire, UK.

Portal pyaemia or pylephlebitis is a form of septic (often suppurative) thrombophlebitis of the portal venous system. It may develop as a complication of intra-abdominal sepsis, such as diverticulitis or appendicitis. Patients typically present with a high fever that is sometimes accompanied by jaundice. Read More

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http://dx.doi.org/10.1136/bcr-2018-228400DOI Listing

Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion.

Hum Genomics 2019 Apr 16;13(1):19. Epub 2019 Apr 16.

Center for Human Disease Modeling, Duke University Medical Center, Carmichael Building, 300 North Duke Street, Suite 48-118, Durham, NC, 27701, USA.

Background: Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases.

Results: We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Read More

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http://dx.doi.org/10.1186/s40246-019-0203-9DOI Listing

Correction to: Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan.

Arthritis Res Ther 2019 Apr 16;21(1):99. Epub 2019 Apr 16.

Division of Rheumatology, Department of Internal Medicine, School of Medicine, Toho University, 2-22-36 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan.

Following publication of the original article [1], the authors reported an error in Table 2. Read More

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http://dx.doi.org/10.1186/s13075-019-1887-xDOI Listing

Dynamic functional connectivity changes in dementia with Lewy bodies and Alzheimer's disease.

Neuroimage Clin 2019 Apr 3;22:101812. Epub 2019 Apr 3.

Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.

We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB. Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101812DOI Listing

Adolescent binge drinking disrupts normal trajectories of brain functional organization and personality maturation.

Neuroimage Clin 2019 Mar 31;22:101804. Epub 2019 Mar 31.

School of Mathematical Sciences, Fudan University, Shanghai 200433, PR China; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, PR China; Department of Computer Science, University of Warwick, Coventry, UK; Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, PR China; Shanghai Center for Mathematical Sciences, Shanghai, PR China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, PR China.

Adolescent binge drinking has been associated with higher risks for the development of many health problems throughout the lifespan. Adolescents undergo multiple changes that involve the co-development processes of brain, personality and behavior; therefore, certain behavior, such as alcohol consumption, can have disruptive effects on both brain development and personality maturation. However, these effects remain unclear due to the scarcity of longitudinal studies. Read More

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http://dx.doi.org/10.1016/j.nicl.2019.101804DOI Listing

Translational drug discovery and development with the use of tissue-relevant biomarkers: towards more physiological relevance and better prediction of clinical efficacy.

Exp Dermatol 2019 Apr 16. Epub 2019 Apr 16.

Sanofi, Global Head of Immunology Therapeutic Research Area, 640 Memorial Drive, Cambridge, MA, 02139, USA.

Due to the clinical development of drugs such as secukinumab, ustekinumab and dupilumab, major changes have been achieved in the treatment of patients diagnosed with psoriasis and atopic dermatitis. In academia and the pharmaceutical industry, research is increasingly moving towards the development of bi-specific antibodies and multi-specific nanobodies, as there is a compelling need for new treatment modalities for patients suffering from auto-immune or malignant disease. The purpose of this review is to discuss aspects of translational drug development with a particular emphasis on indications such as psoriasis and atopic dermatitis. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/exd.13942
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http://dx.doi.org/10.1111/exd.13942DOI Listing
April 2019
2 Reads

Inter-brand competition in the convenience store industry, store density and healthcare utilization.

J Health Econ 2019 Mar 25;65:117-132. Epub 2019 Mar 25.

College of Business and Economics, Lehigh University, Bethlehem, United States; National Bureau of Economic Research, Cambridge, United States. Electronic address:

We investigate the impact of access to convenience stores and competition between convenience store chains on the use of medical care in Taiwan. Using insurance claims from 0.85 million individuals and administrative data on store sales, we find that greater store density and more inter-brand competition reduced expenditures on outpatient medical services and prescription drugs. Read More

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http://dx.doi.org/10.1016/j.jhealeco.2019.03.001DOI Listing

Genetic Counselling to Genomic Counselling: an evolution not revolution.

Eur J Med Genet 2019 Apr 13. Epub 2019 Apr 13.

Wellcome Genome Campus, Society and Ethics Research Group, Connecting Science, Hinxton, Cambridge; Faculty of Education, University of Cambridge, Cambridge; Chair of the Association of Genetic Nurses and Counsellors (2018/2019), UK and Republic of Ireland. Electronic address:

Genome sequencing as a technology is rapidly transitioning from research into healthcare. By 2025 over 60 million patients across the globe will have their genomes sequenced in a healthcare setting [1]. 'Genomic medicine', could also now just be called 'Medicine' with the added benefit of genomic technology available as part of the patient testing repertoire. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.010DOI Listing